NU 7441

NU7441, also known as KU-57788, is a highly potent and selective DNA-PK inhibitor (IC50=14 nM), exhibiting ATP-competitive inhibition kinetics. NU7441 increased the cytotoxicity of ionizing radiation and etoposide in SW620, LoVo, and V3-YAC cells but not in V3 cells, confirming that potentiation was due to DNA-PK inhibition. NU7441 substantially retarded the repair of ionizing radiation-induced and etoposide-induced DSB.

Product information

CAS Number: 503468-95-9

Molecular Weight: 413.49

Formula: C25H19NO3S

Synonym:

NU-7441

KU-57788

NU7441

NU 7441

KU 57788

KU57788

Chemical Name: 8-(4-dibenzothienyl)-2-(4-morpholinyl)-4H-1-benzopyran-4-one

Smiles: O=C1C=C(OC2=C1C=CC=C2C1=CC=CC2=C1SC1=CC=CC=C21)N1CCOCC1

InChiKey: JAMULYFATHSZJM-UHFFFAOYSA-N

InChi: InChI=1S/C25H19NO3S/c27-21-15-23(26-11-13-28-14-12-26)29-24-17(6-3-9-20(21)24)19-8-4-7-18-16-5-1-2-10-22(16)30-25(18)19/h1-10,15H,11-14H2

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not in water

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

KU-57788 (0.5 to 10 µM) inhibits the growth of liver cancer HepG2 cells dose- and time-dependently. KU-57788 reduces pDNA-PKcs (S2056) protein expression in liver cancer cells. Furthermore, double treatment of KU-57788 and 60Coγ IR affects DNA damage repair. KU-57788 weakly inhibits BRD4 and BRDT with IC50s of 1 μM and 3.5 μM, respectively. KU-57788 is solvent-exposed in BRD4, this inhibitor can be classified as a Type I BRD inhibitor. KU-57788 reduces the frequency of NHEJ while increasing the rate of HDR following Cas9-mediated DNA cleavage.

References:

1. Tichy A, Durisova K, Salovska B, Pejchal J, Zarybnicka L, Vavrova J, Dye NA, Sinkorova Z. Radio-sensitization of human leukaemic MOLT-4 cells by DNA-dependent protein kinase inhibitor, NU7441. Radiat Environ Biophys. 2013 Oct 8. [Epub ahead of print] PubMed PMID: 24100951.
2. Tavecchio M, Munck JM, Cano C, Newell DR, Curtin NJ. Further characterisation of the cellular activity of the DNA-PK inhibitor, NU7441, reveals potential cross-talk with homologous recombination. Cancer Chemother Pharmacol. 2012 Jan;69(1):155-64. doi: 10.1007/s00280-011-1662-4. Epub 2011 Jun 1. PubMed PMID: 21630086.
3. Zhao Y, Thomas HD, Batey MA, Cowell IG, Richardson CJ, Griffin RJ, Calvert AH, Newell DR, Smith GC, Curtin NJ. Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Res. 2006 May 15;66(10):5354-62. PubMed PMID: 16707462.

Products are for research use only. Not for human use.